Children represent less than 1% of all solid cancers of unknown primary site. Because of the age-related incidence of tumor types, embryonal histologies are more common in children.
Cancers of unknown primary site present as a metastatic cancer for which a precise primary tumor site cannot be determined. As an example, lymph nodes at the base of the skull may enlarge in relationship to a tumor that may be on the face or the scalp but is not evident by physical examination or by radiographic imaging. Thus, modern imaging techniques may indicate the extent of the disease but not a primary site. Tumors such as adenocarcinomas, melanomas, and embryonal tumors, like rhabdomyosarcomas and neuroblastomas, may present in this way.
For all patients who present with tumors from an unknown primary site, treatment is directed toward the specific histopathology of the tumor and is age-appropriate for the general type of cancer initiated, irrespective of the site or sites of involvement.
Studies in adults suggest that positron emission tomography (PET) imaging can be helpful in identifying cancers of unknown primary site, particularly in patients whose tumors arise in the head and neck area. A report in adults using fluorine F 18-fludeoxyglucose (18F-FDG) PET-computed tomography (CT) identified 42.5% of primary tumors in a group of cancers of unknown primary site.
The use of gene expression profiling and next-generation sequencing can enhance the ability to identify the putative tissue of origin and guide in the selection of targeted agents for specific mutations.[4,5,6,7,8] In a study of 200 adult patients with carcinomas of unknown primary site, 125 had adenocarcinomas and 75 had carcinomas without features of adenocarcinoma. Genomic alterations were found in 96% of the cases. The most common alterations were TP53 (55%), KRAS (20%), CDKN2A (19%), and MYC (12%). Clinically relevant and potentially actionable mutations included KRAS (20%), CDKN2A (19%), MCL1 (10%), PTEN (7%), PIK3CA (9%), ERBB2 (8%), RICTOR (6%), BRAF (6%), and NF1 (4%). These findings suggest that genomic profiling can help identify potentially actionable targets that could provide clinical benefit for these patients while reducing the complex and costly workup needed to search for a primary tumor site of origin. Despite reports of precision medicine studies in pediatric oncology, none of them have described a case of carcinoma of unknown primary site with a defined or actionable genomic alteration.
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years. The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people. Therefore, all pediatric cancers are considered rare.
The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[5,6] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:
Most cancers in subgroup XI are either melanomas or thyroid cancer, with other types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer, such as the PDQ summary on Carcinoma of Unknown Primary Treatment.
Chemotherapy, targeted therapy, and radiation therapy treatments appropriate and relevant for the general category of carcinoma or sarcoma (depending on the histological findings, symptoms, and extent of tumor) are initiated as early as possible.
(Refer to the PDQ summary on adult Carcinoma of Unknown Primary Treatment for more information.)
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric carcinoma of unknown primary. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Carcinoma of Unknown Primary Treatment are:
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Carcinoma of Unknown Primary Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/unknown-primary/hp/child-unknown-primary-treatment-pdq. Accessed <MM/DD/YYYY>.
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Last Revised: 2022-02-23
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